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Journal of Amino Acids
Volume 2012 (2012), Article ID 691463, 6 pages
http://dx.doi.org/10.1155/2012/691463
Research Article

In Vitro Activities of Kissorphin, a Novel Hexapeptide KiSS-1 Derivative, in Neuronal Cells

Department of Human and Health Sciences, School of Life Sciences, University of Westminster, London W1W 6UW, UK

Received 31 March 2012; Accepted 11 June 2012

Academic Editor: Dorothy Gietzen

Copyright © 2012 Nathaniel G. N. Milton. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The primary products of the metastasis-suppressor KiSS-1 gene are the kisspeptin (KP) peptides that stimulate gonadotrophin-releasing-hormone (GnRH) release via GPR-54 receptor activation. Recent studies have suggested that the KP-10 peptide also activates neuropeptide FF (NPFF) receptors. The aim of the current study was to determine the activities of the KiSS-1 derivative kissorphin (KSO), which contains the first six amino acids of the KP-10 peptide, is C-terminally amidated, and shares amino acid similarities with the biologically active NPFF 3–8 sequence. The KSO peptide inhibited forskolin-stimulated cyclic adenosine monophosphate (cAMP) production in ND7/23 neuroblastoma cells via an action that could be inhibited by the NPFF receptor antagonist RF9. Release of GnRH by LA-N-1 neuroblastoma cells was not altered by the KSO peptide. In ND7/23 neuroblastoma cells, the KSO peptide was able to reduce forskolin neuroprotection against H2O2 toxicity. The KSO peptide was also able to prevent prostaglandin E2-induced apoptosis in rat cortical neurons. The NPFF receptor antagonist RF9 could inhibit these actions of the KSO peptide in oxidative stress and apoptosis models. In conclusion, the kissorphin peptide, comprising the amino acid sequence Tyr-Asn-Trp-Asn-Ser-Phe-NH2, has NPFF-like biological activity without showing any GnRH releasing activity and inhibits forskolin-activated cAMP release.